TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35637	107134;107135;107136	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
N2AB	33996	102211;102212;102213	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
N2A	33069	99430;99431;99432	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
N2B	26572	79939;79940;79941	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
Novex-1	26697	80314;80315;80316	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
Novex-2	26764	80515;80516;80517	chr2:178528842;178528841;178528840	chr2:179393569;179393568;179393567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-167
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.4359
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/N	rs767045071	None	0.782	N	0.563	0.202	0.154104182512	gnomAD-4.0.0	1.91561E-05	None	None	None	None	N	None	5.97372E-05	0	None	0	0	None	0	0	2.33843E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.683	likely_pathogenic	0.7556	pathogenic	-0.547	Destabilizing	0.575	D	0.573	neutral	None	None	None	None	N
K/C	0.8862	likely_pathogenic	0.9138	pathogenic	-0.508	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.9078	likely_pathogenic	0.9467	pathogenic	-0.187	Destabilizing	0.826	D	0.653	neutral	None	None	None	None	N
K/E	0.4173	ambiguous	0.527	ambiguous	-0.047	Destabilizing	0.338	N	0.547	neutral	N	0.472643017	None	None	N
K/F	0.9247	likely_pathogenic	0.941	pathogenic	-0.064	Destabilizing	0.906	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.8423	likely_pathogenic	0.8893	pathogenic	-0.945	Destabilizing	0.575	D	0.645	neutral	None	None	None	None	N
K/H	0.4882	ambiguous	0.5063	ambiguous	-1.252	Destabilizing	0.906	D	0.681	prob.neutral	None	None	None	None	N
K/I	0.562	ambiguous	0.6047	pathogenic	0.5	Stabilizing	0.879	D	0.715	prob.delet.	N	0.475590108	None	None	N
K/L	0.6021	likely_pathogenic	0.6349	pathogenic	0.5	Stabilizing	0.575	D	0.645	neutral	None	None	None	None	N
K/M	0.4365	ambiguous	0.4767	ambiguous	0.268	Stabilizing	0.991	D	0.672	neutral	None	None	None	None	N
K/N	0.695	likely_pathogenic	0.7822	pathogenic	-0.569	Destabilizing	0.782	D	0.563	neutral	N	0.474896675	None	None	N
K/P	0.9884	likely_pathogenic	0.994	pathogenic	0.182	Stabilizing	0.906	D	0.668	neutral	None	None	None	None	N
K/Q	0.2247	likely_benign	0.2517	benign	-0.529	Destabilizing	0.782	D	0.584	neutral	N	0.474203242	None	None	N
K/R	0.1203	likely_benign	0.1197	benign	-0.734	Destabilizing	0.001	N	0.247	neutral	N	0.444920485	None	None	N
K/S	0.6728	likely_pathogenic	0.7511	pathogenic	-1.162	Destabilizing	0.575	D	0.526	neutral	None	None	None	None	N
K/T	0.298	likely_benign	0.3692	ambiguous	-0.807	Destabilizing	0.505	D	0.625	neutral	N	0.47333645	None	None	N
K/V	0.5731	likely_pathogenic	0.6069	pathogenic	0.182	Stabilizing	0.826	D	0.657	neutral	None	None	None	None	N
K/W	0.9383	likely_pathogenic	0.9547	pathogenic	0.007	Stabilizing	0.991	D	0.672	neutral	None	None	None	None	N
K/Y	0.8531	likely_pathogenic	0.8803	pathogenic	0.275	Stabilizing	0.906	D	0.717	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.